EXPRESSION AND MUTATION OF THE TUMOR-SUPPRESSOR GENE P53 IN AIDS-ASSOCIATED KAPOSIS-SARCOMA

Alteration of the p53 gene is the most frequent event reported in huma n cancer, and p53 mutations have been observed in various neoplasms, i ncluding certain forms of skin cancer. Therefore, we postulated that p 53 may also be involved in Kaposi's sarcoma associated with AIDS (AIDS -KS). Expression of the p53 gene was examined in freshly isolated tumo r biopsy specimens from 15 patients with AIDS-KS. p53 mRNA was detecte d by reverse transcriptase-polymerase chain reaction (RT-PCR) in both the AIDS-KS tumors and in normal skin control samples. p53 protein was detected in 4 of the 15 AIDS-KS specimens by immunohistochemical stai ning. Single-strand conformation polymorphism analysis PCR-products (P CR-SSCP) was used for detection of mutations of the p53 gene. One of t he p53 positive AIDS-KS samples showed mobilized shifts in exon 6 sugg estive of a mutation. Sequencing data showed the mutation to be locate d in codon 210. We examined other mechanisms that could stabilize p53 protein. SV40 large T antigen and adenovirus E1B protein were not foun d in the AIDS-KS specimens. MDM2, a p53-binding protein, was also dete cted in five of the AIDS-KS specimens, two of which also contained p53 -positive cells. These observations suggest that the tumor suppressor gene p53 may be involved in the pathogenesis of AIDS-KS.